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CAR -T autoimmune disease

Roy L Kao, Laurel C Truscott, Tzu-Ting Chiou, Wenting Tsai, Anna M Wu, Satiro N De Oliveira
BACKGROUND: We propose using gene-modification of HSC to create persistent generation of multilineage immune effectors to directly target cancer cells. Gene-modified human hematopoietic stem cells (HSC) have been used to introduce genes to correct, prevent or treat diseases. Concerns regarding malignant transformation, abnormal hematopoiesis and autoimmunity exist, making the co-delivery of a suicide gene a necessary safety measure. We tested truncated epidermal growth factor receptor (EGFRt) as a suicide gene system co-delivered with anti-CD19 chimeric antigen receptor (CAR) to human HSC...
March 12, 2019: Human Gene Therapy
Alejandro Carazo, Jan Dusek, Ondrej Holas, Josef Skoda, Lucie Hyrsova, Tomas Smutny, Tomas Soukup, Martin Dosedel, Petr Pávek
The constitutive androstane receptor (CAR) is a nuclear receptor involved mainly in xenobiotic and endobiotic metabolism regulation. CAR is activated directly by its ligands via the ligand binding domain (LBD) or indirectly by inhibition of the epidermal growth factor (EGF) signaling. We found that leflunomide (LEF) and its main metabolite teriflunomide (TER), both used for autoimmune diseases treatment, induce the prototype CAR target gene CYP2B6 in primary human hepatocytes. As TER was discovered to be an EGF receptor antagonist, we sought to determine if TER is an indirect activator of CAR...
2018: Frontiers in Pharmacology
Yue Yang, Yang Wang, Yawei Kong, Xiaoning Zhang, He Zhang, Yi Gang, Lunhao Bai
Background: The anti-inflammatory and antioxidant capacity of carnosine (CAR) has been investigated in autoimmune diseases. The aim of this study was to evaluate the potential protective effects of oral CAR supplements to ameliorate type 2 diabetes mellitus (T2DM)-induced osteoarthritis (OA) in rats and its mechanism. Methods: Seventy male Sprague-Dawley rats were randomly divided into the control group (CG, n = 10) and the T2DM group ( n = 60). A rat model of T2DM was established using a high fat diet and streptozotocin (30 mg/kg, i...
2018: Frontiers in Pharmacology
William J Taylor, Ketna Parekh
BACKGROUND: Versions of the Health Assessment Questionnaire (HAQ) are commonly used to measure physical functioning across multiple rheumatic diseases but there has been no clear demonstration that any HAQ version is actually generic. This study aimed to show that the HAQ-II instrument is invariant across different rheumatic disease categories using the Rasch measurement model, which would confirm that the instrument is generic. METHODS: HAQ-II responses from 882 consecutive rheumatology clinic attendees were fitted to a Rasch model...
May 30, 2018: Health and Quality of Life Outcomes
Grazyna Adamus
Autoantibodies (AAbs) against various retinal proteins have been associated with vision loss in paraneoplastic and non-paraneoplastic autoimmune retinopathies (AR). There are two major paraneoplastic syndromes associated anti-retinal AAbs, cancer-associated retinopathy (CAR), and melanoma-associated retinopathy. Some people without a cancer diagnosis may present symptoms of CAR and have anti-retinal AAbs. The etiology and pathogenesis of those entities are not fully understood. In this review, we provide evidence for the role of AAbs in retinal death and degeneration...
2018: Frontiers in Immunology
Wanessa da Silva Silveira, Ezequiel Gregolin Bottezini, Maria Salete Linden, Isadora Rinaldi, Luiz Renato Paranhos, João Paulo de Carli, Micheline Trentin, Pâmela Letícia Dos Santos
Lichen planus (LP) is a relatively common mucocutaneous disease with autoimmune etiology. Considering its malignancy potential, it is important to define the correct diagnosis, treatment, and clinical follow-up for patients with LP so that the disease is not diagnosed late, thus hindering the chances of curing the disease. This study aims to describe a clinical case of oral squamous cell carcinoma, potentially originated from LP. The patient is undergoing clinical and histopathological follow-up. A 64-year-old Caucasian male patient presented with a proliferative verrucous lesion on the tongue and sought treatment at the School of Dentistry, University of Passo Fundo (UPF), Passo Fundo, Brazil...
December 2017: Journal of the Korean Association of Oral and Maxillofacial Surgeons
Aristófanes Mendonça Canamary, Walter Yukihiko Takahashi, Juliana Maria Ferraz Sallum
Autoimmune retinopathy (AIR) is a rare and still poorly understood immune-mediated disease that may cause inflammation from circulating autoantibodies against the retina. It may be related to history of autoimmune disease in the patient or in a family member or the presence of neoplastic disease in the individual. The disease may be subdivided into paraneoplastic and non-paraneoplastic AIR. When related to melanoma, it is referred to as MAR, and when related to other cancers, it is called CAR. The exact prevalence of AIR is unknown...
2018: International Journal of Retina and Vitreous
Attila Ozsvár, Róbert Szipőcs, Zoltán Ozsvár, Judith Baka, Pál Barzó, Gábor Tamás, Gábor Molnár
Degradation of myelin sheath is thought to be the cause of neurodegenerative diseases, such as multiple sclerosis (MS), but definitive agreement on the mechanism of how myelin is lost is currently lacking. Autoimmune initiation of MS has been recently questioned by proposing that the immune response is a consequence of oligodendrocyte degeneration. To study the process of myelin breakdown, we induced demyelination with cuprizone and applied coherent anti-Stokes Raman scattering (CARS) microscopy, a non-destructive label-free method to image lipid structures in living tissue...
March 2018: Brain Research Bulletin
Grazyna Adamus
Autoantibodies (AAbs) against glycolytic enzymes: aldolase, α-enolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase are prevalent in sera of patients with blinding retinal diseases, such as paraneoplastic [cancer-associated retinopathy (CAR)] and non-paraneoplastic autoimmune retinopathies, as well as in many other autoimmune diseases. CAR is a degenerative disease of the retina characterized by sudden vision loss in patients with cancer and serum anti-retinal AAbs. In this review, we discuss the widespread serum presence of anti-glycolytic enzyme AAbs and their significance in autoimmune diseases...
2017: Frontiers in Immunology
Maria Buoncervello, Matteo Marconi, Alessandra Carè, Paola Piscopo, Walter Malorni, Paola Matarrese
The biology of sex differences deals with the study of the disparities between females and males and the related biological mechanisms. Gender medicine focuses on the impact of gender and sex on human physiology, pathophysiology and clinical features of diseases that are common to women and men. The term gender refers to a complex interrelation and integration of sex-as a biological and functional determinant-and psychological and cultural behaviours (due to ethnical, social or religious background). The attention to the impact of gender differences on the pathophysiology and, therefore, on the clinical management of the most common diseases, such as cardiovascular diseases (CVD), neurodegenerative disorders, immune and autoimmune diseases as well as several tumours, is in fact often neglected...
March 1, 2017: Clinical Science (1979-)
Laura B Lewandowski, Melissa H Watt, Laura E Schanberg, Nathan M Thielman, Christiaan Scott
BACKGROUND: Systemic Lupus Erythematosus (SLE) is a serious multisystem autoimmune disease, which is more aggressive in children and people of African descent. In South Africa, pediatric SLE (pSLE) patients are at high risk for severe disease. Similar to pSLE worldwide, South African children and adolescents with SLE require subspecialized medical care. The aim of this study is to describe the care-seeking experiences of families and examine factors that contribute to delays in the diagnosis of pSLE...
February 23, 2017: Pediatric Rheumatology Online Journal
Cínthia Magalhães Ribeiro, Clenivaldo Alves Caixeta, Marina Lara de Carli, Felipe Fornias Sperandio, Evandro Monteiro de Sá Magalhães, Alessandro Antônio Costa Pereira, João Adolfo Costa Hanemann
Paracoccidioidomycosis (PCM) is a systemic disease caused by the dimorphic fungus Paracocdioides brasiliensis. The infection primarily reaches the lungs by the inhalation of fungi spores and later can disseminate to other organs causing secondary oral lesions. Systemic lupus erythematosus (SLE), on the other hand, is an autoimmune chronic inflammatory disease that affects various organ systems, including skin and oral cavity. Here we report a 39-year-old female patient bearing SLE and presenting an ulcerated lesion on the hard palate extending to the superior alveolar ridge, diagnosed as PCM...
March 2017: Photodiagnosis and Photodynamic Therapy
Shiv Kumar Sarin, Ashok Choudhury
Acute-on-chronic liver failure (ACLF) is a distinct entity that differs from acute liver failure and decompensated cirrhosis in timing, presence of treatable acute precipitant, and course of disease, with a potential for self-recovery. The core concept is acute deterioration of existing liver function in a patient of chronic liver disease with or without cirrhosis in response to an acute insult. The insult should be a hepatic one and presentation in the form of liver failure (jaundice, encephalopathy, coagulopathy, ascites) with or without extrahepatic organ failure in a defined time frame...
December 2016: Current Gastroenterology Reports
Mübeccel Akdis, Alar Aab, Can Altunbulakli, Kursat Azkur, Rita A Costa, Reto Crameri, Su Duan, Thomas Eiwegger, Andrzej Eljaszewicz, Ruth Ferstl, Remo Frei, Mattia Garbani, Anna Globinska, Lena Hess, Carly Huitema, Terufumi Kubo, Zsolt Komlosi, Patricia Konieczna, Nora Kovacs, Umut C Kucuksezer, Norbert Meyer, Hideaki Morita, Judith Olzhausen, Liam O'Mahony, Marija Pezer, Moira Prati, Ana Rebane, Claudio Rhyner, Arturo Rinaldi, Milena Sokolowska, Barbara Stanic, Kazunari Sugita, Angela Treis, Willem van de Veen, Kerstin Wanke, Marcin Wawrzyniak, Paulina Wawrzyniak, Oliver F Wirz, Josefina Sierra Zakzuk, Cezmi A Akdis
There have been extensive developments on cellular and molecular mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections during the last few years. Better understanding the functions, reciprocal regulation, and counterbalance of subsets of immune and inflammatory cells that interact through interleukins, interferons, TNF-α, and TGF-β offer opportunities for immune interventions and novel treatment modalities in the era of development of biological immune response modifiers particularly targeting these molecules or their receptors...
October 2016: Journal of Allergy and Clinical Immunology
Sufang Yang, Alexander Dizhoor, David J Wilson, Grazyna Adamus
PURPOSE: Autoantibodies (AAbs) with different retinal specificities were reported in cancer-associated retinopathy (CAR) and autoimmune retinopathy (AR). The goal was to identify the small retinal proteins of apparent molecular mass of 23-kDa often recognized by patients' AAbs. METHODS: Sera specific for a 23-kDa retinal protein of 173 patients were investigated retrospectively by Western blotting and double immunofluorescence confocal microscopy. A proteomic analysis revealed new 23-kDa protein candidates, including guanylyl cyclase-activating proteins (GCAPs), heat shock protein 27 (HSP27), and Rab6A GTPase (Rab6A)...
May 2016: Translational Vision Science & Technology
Barbara Frossi, Stefano De Carli, Fleur Bossi, Carlo Pucillo, Marco De Carli
BACKGROUND: Immunoglobulin (Ig) A deficiency is a primary immunodeficiency in which autoimmunity is frequently observed. Thirty to fifty percent of patients with spontaneous chronic urticaria have autoantibodies that are able to cross-link FcεRI on mast cells and basophils. METHODS: We investigated whether spontaneous chronic urticaria in patients with IgA deficiency meets the criteria for autoimmunity. Four patients were screened for positivity to a skin prick test and an autologous serum skin test and for the presence of other autoimmune diseases...
2016: International Archives of Allergy and Immunology
Gehan Ahmed Mostafa, Geir Bjørklund, Mauricio A Urbina, Laila Yousef Al-Ayadhi
Tachykinins (substance P, neurokinin A, and neurokinin B) are pro-inflammatory neuropeptides that may play an important role in some autoimmune neuroinflammatory diseases, including autism spectrum disorder (ASD). Mercury (Hg) is a neurotoxicant, and potentially one of the main environmental triggers for ASD as it induces neuroinflammation with a subsequent release of neuropeptides. This is the first study to explore the potentially causal relationship between levels of serum neurokinin A and blood mercury (BHg) in children with ASD...
June 2016: Metabolic Brain Disease
Maro Bujak, Ivana Ratkaj, Elitza Markova-Car, Davor Jurišić, Anita Horvatić, Srđan Vučinić, Jonatan Lerga, Mirela Baus-Lončar, Krešimir Pavelić, Sandra Kraljević Pavelić
OBJECTIVES: Inflammation is an underlying mechanism behind fibrotic processes and differentiation of cells into myofibroblasts. Presented study therefore provides new data on activation of autoimmune and inflammatory immune response genes that accompany activation of p38 and cell differentiation in primary cells derived from Dupuytren's disease (DD) patients. METHODS: Primary non-Dupuytren's disease cells (ND) were isolated from macroscopically unaffected palmar fascia adjacent to diseased tissue obtained from patients diagnosed with the last stage of DD and cultured in vitro...
2015: Frontiers in Molecular Biosciences
J H Salmon, P Cacoub, B Combe, J Sibilia, B Pallot-Prades, O Fain, A Cantagrel, M Dougados, E Andres, O Meyer, P Carli, E Pertuiset, I Pane, F Maurier, P Ravaud, X Mariette, J E Gottenberg
OBJECTIVES: To evaluate the prevalence of late-onset neutropenia and its complications in patients treated with rituximab (RTX) for rheumatoid arthritis (RA) and other autoimmune diseases (AIDs) in a prospective registry. METHODS: The AutoImmunity and Rituximab registry is an independent 7-year prospective registry promoted by the French Society of Rheumatology. For each episode of neutropenia, data were validated by the clinician in charge of the patient. RESULTS: Among 2624 patients treated with RTX for refractory AIDs, and at least 1 follow-up visit (a total follow-up of 4179 patient-years in RA and 987 patient-years in AIDs), late-onset neutropenia was observed in 40 patients (25 RA (1...
2015: RMD Open
Carly S Gardner, Mustafa R Bashir, Daniele Marin, Rendon C Nelson, Kingshuk Roy Choudhury, Lisa M Ho
OBJECTIVE: To determine the diagnostic performance of imaging criteria for distinguishing Ig-G4-associated autoimmune cholangiopathy (IAC) from primary sclerosing cholangitis (PSC) and bile duct malignancy. METHODS: A medical records search between January 2008 and October 2013 identified 10 patients (8 M, 2 F, mean age 61 years, range 34-82) with a clinical diagnosis of IAC. Fifteen cases of PSC (6 M, 9 F, mean age 50, range 22-65) and 15 cases of biliary malignancy (7 M, 8 F, mean age 65, range 48-84) were randomly selected for comparative analysis...
October 2015: Abdominal Imaging
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